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Liposome-supported enzymatic peritoneal dialysis
Biomaterials ( IF 14.0 ) Pub Date : 2017-08-14 , DOI: 10.1016/j.biomaterials.2017.08.016
Anna Pratsinis , Stefanie Zuercher , Vincent Forster , Eric J. Fischer , Paola Luciani , Jean-Christophe Leroux

Compared to hemodialysis, peritoneal dialysis represents a more straightforward and less invasive alternative, though current solutions are not as effective. Herein, the feasibility of liposome-supported enzymatic peritoneal dialysis (LSEPD) is explored to increase the functionality of peritoneal dialysis for the model indication acute alcohol poisoning. Enzyme-loaded liposomes (E-Liposomes) containing alcohol metabolizing enzymes, alcohol oxidase and catalase, are developed and their in vitro and in vivo performances investigated. The E-Liposomes outperform the free enzymes in stability, overcoming the thermal instability of alcohol oxidase and enhancing the in vitro ethanol elimination, which is further accelerated by hydrogen peroxide, due to the rapid generation of oxygen by catalase. Compared to the free enzymes, the E-Liposomes exhibit reduced systemic exposure and organ distribution. In a rodent ethanol intoxication model, LSEPD enhances ethanol metabolism as evidenced by an increased acetaldehyde production, ethanol's primary metabolite. In conclusion, LSEPD presents an innovative platform to temporarily enhance xenobiotic metabolism, in view of the improved enzyme stability and peritoneal retention.

中文翻译:

脂质体支持的酶促腹膜透析

与血液透析相比,腹膜透析代表了一种更直接,侵入性更小的替代方法,尽管目前的解决方案并不那么有效。在此,探索脂质体支持的酶促腹膜透析(LSEPD)的可行性,以增加模型指示急性酒精中毒的腹膜透析功能。开发了含有酒精代谢酶,酒精氧化酶和过氧化氢酶的酶负载脂质体(E-脂质体),并研究了它们的体外体内性能。E-脂质体在稳定性方面优于游离酶,克服了醇氧化酶的热不稳定性并增强了体外由于过氧化氢酶可迅速产生氧气,因此乙醇的消除会被过氧化氢进一步加速。与游离酶相比,E-脂质体表现出降低的全身暴露和器官分布。在啮齿动物乙醇中毒模型中,LSEPD增强了乙醇的新陈代谢,乙醛产量(乙醇的主要代谢产物)的增加证明了这一点。总之,鉴于改善的酶稳定性和腹膜滞留性,LSEPD提供了一个创新平台,可暂时增强异种生物的代谢。
更新日期:2017-08-17
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